DRAFT - DO NOT CITE OR QUOTE lNCEA tradan" dr"f's or EPA ID for final] www.epa.gov/iris 4>EPA ANNOTATED REFERENCE OUTLINE FOR THE TOXICOLOGICAL REVIEW OF 2,3,4-T rimethylpentane (CAS No. 565-75-3) In Support of Summary Information on the Integrated Risk Information System (IRIS) 12/22/08 [author: insert current date for this draft or Agency completion date (month and year) iffinal] NOTICE This document is a [author: insert Agency Review or external review] draft. It has not been formally released by the U.S. Environmental Protection Agency and should not at this stage be construed to represent Agency position on this chemical. It is being circulated for review of its technical accuracy and science policy implications. U.S. Environmental Protection Agency Washington, DC ------- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 REVIEWS Abraham, MH; Ibrahim, A. (2006) Air to fat and blood to fat distribution of volatile organic compounds and drugs: Linear free energy analyses. European Journal of Medicinal Chemistry 41(12): 1430-1438. Abraham, MH; Ibrahim, A; Acree, WE, Jr. (2005) Air to blood distribution of volatile organic compounds: A linear free energy analysis. Chem Res Toxicol 18:904-911. ACGIH. (2001) Octane, all isomers. ACGIH. Documentation of the threshold limit values and biological exposure indices Cincinnati, OH: American Conference of Governmental Industrial Hygienists; p. 2. ACGIH. (2007) Octane, all isomers. Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists; p. 45. Carreon, T (2001) Aliphatic hydrocarbons. In: Bingham, E; Cohrssen, B; Powell, CH; et al.; eds. Patty's toxicology. John Wiley & Sons, Inc. 2. CHEMICAL AND PHYSICAL INFORMATION Wilson, EW, Jr.; Hamilton, WA; Kennington, HR; et al. (2006) Measurement and estimation of rate constants for the reactions of hydroxyl radical with several alkanes and cycloalkanes. J Phys Chem A 110(10):3593-3604. 3. TOXICOKINETICS 3.1. ABSORPTION American Petroleum Institute. (1987) Studies on the absorption of inhaled hydrocarbon vapors (final report). Submitted under TSCA section FYI; NTIS no. OTS0000488. Dahl, AR; Damon, EG; Mauderly, JL; et al. (1988) Uptake of 19 hydrocarbon vapors inhaled by f344 rats. Fundam Appl Toxicol 10(2):262-269. 3.2. DISTRIBUTION Abraham, MH; Ibrahim, A. (2006) Air to fat and blood to fat distribution of volatile organic compounds and drugs: Linear free energy analyses. European Journal of Medicinal Chemistry 41(12): 1430-1438. Abraham, MH; Ibrahim, A; Acree, WE, Jr. (2005) Air to blood distribution of volatile organic compounds: A linear free energy analysis. Chem Res Toxicol 18:904-911. 10/8/2009 B-2 DO NOT CITE OR QUOTE ------- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 Meulenberg, CJ; Vijverberg, HP. (2000) Empirical relations predicting human and rat tissue: Air partition coefficients of volatile organic compounds. Toxicol Appl Pharmacol 165(3):206-216. 3.3. METABOLISM Delraso, NJ; Mattie, DR; Godin, CS. (1989) In vitro toxicity of solubilized 2,3,4- trimethylpentane. I. Cytotoxicity and metabolism of tmp using primary hepatocytes. In Vitro Cell Dev Biol 25(11): 1031-1038. DelRaso, NJ; Mattie, DR; Godin, CS. (1990) Lack of detectable metabolism for solubilized 2,3,4-trimethylpentane by rat kidney proximal tubules. Toxicol Lett 54(2-3):337-344. Olson, CT; Hobson, DW; Yu, KO; et al. (1987) The metabolism of 2,3,4-trimethylpentane in male fischer-344 rats. Toxicol Lett 37(3): 199-202. Yu, KO; Olson, CT; Hobson, DW; et al. (1987) Identification of urinary metabolites in rats exposed to the nephrotoxic agent 2,3,4-trimethylpentane. Biomed Environ Mass Spectrom 14(11):639-641. 3.4. ELIMINATION Olson, CT; Hobson, DW; Yu, KO; et al. (1987) The metabolism of 2,3,4-trimethylpentane in male fischer-344 rats. Toxicol Lett 37(3): 199-202. Phillips, M; Greenberg, J; Awad, J. (1994) Metabolic and environmental origins of volatile organic compounds in breath. Journal of Clinical Pathology (London) 47(11): 1052-1053. Phillips, M; Herrera, J; Krishnan, S; et al. (1999) Variation in volatile organic compounds in the breath of normal humans. Journal of Chromatography B 729(l-2):75-88. Yu, KO; Olson, CT; Hobson, DW; et al. (1987) Identification of urinary metabolites in rats exposed to the nephrotoxic agent 2,3,4-trimethylpentane. Biomed Environ Mass Spectrom 14(11):639-641. 3.5. PHYSIOLOGICALLY BASED TOXICOKINETIC MODELS 4. HAZARD IDENTIFICATION 4.1. STUDIES IN HUMANS—EPIDEMIOLOGY, CASE REPORTS, CLINICAL CONTROLS 10/8/2009 B-3 DO NOT CITE OR QUOTE ------- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 4.2. LESS-THAN-LIFETIME AND CHRONIC STUDIES AND CANCER BIOASSAYS IN ANIMALS—ORAL AND INHALATION 4.2.1. Oral Bruner, RH; Pitts, LL (1983) Nephrotoxicity of hydrocarbon propellants to male, Fischer-344 rats. Available online at http://handle.dtic.mi1/100.2/ADP001983. Accessed on December 17, 2008. Norton, WN; Mattie, DR. (1987) The cytotoxic effects of trimethylpentane on rat renal tissue. Scanning Microsc l(2):783-790. 4.2.2. Inhalation 4.3. REPRODUCTIVE/DEVELOPMENTAL STUDIES—ORAL AND INHALATION 4.4. OTHER ENDPOINT-SPECIFIC STUDIES Delraso, NJ; Mattie, DR; Godin, CS. (1989) In vitro toxicity of solubilized 2,3,4- trimethylpentane. I. Cytotoxicity and metabolism of tmp using primary hepatocytes. In Vitro Cell Dev Biol 25(11): 1031-1038. DelRaso, NJ; Mattie, DR; Godin, CS. (1990) Lack of detectable metabolism for solubilized 2,3,4-trimethylpentane by rat kidney proximal tubules. Toxicol Lett 54(2-3):337-344. Mattie, DR; Maslanka, JJ; DelRaso, NJ; et al. (1989) Effect of 2,3,4-trimethylpentane on the ultrastructure of proximal tubular cells in primary cell culture. U.S. Department of Commerce. Washington, DC. NTIS/ADA359960. 4.4.1. ACUTE AND SHORT-TERM TOXICITY 4.4.2. GENOTOXICITY STUDIES 4.4.3. NEUROTOXICITY STUDIES 4.4.4. ENDOCRINE DISRUPTION 4.4.5. CONTACT SENSITIZATION 10/8/2009 B-4 DO NOT CITE OR QUOTE ------- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 4.5. MECHANISTIC DATA AND OTHER STUDIES IN SUPPORT OF THE MODE OF ACTION Aschmann, SM; Arey, J; Atkinson, R. (2004) Products and mechanism of the reaction of OH radicals with 2,3,4-trimethylpentane in the presence of no. Environ Sci Technol 38(19):5038- 5045. 4.6. SYNTHESIS OF MAJOR NONCANCER EFFECTS 4.6.1. Oral 4.6.2. Inhalation 4.6.3. Mode of Action Information 4.7. EVALUATION OF CARCINOGENICITY 4.7.1. Summary of Overall Weight-of-Evidence 4.7.2. Synthesis of Human, Animal, and Other Supporting Evidence 4.7.3. Mode of Action Information 4.7.2.1. Hypothesized Mode of Action 4.7.2.2. Experimental Support for the Hypothesized Mode of Action 4.7.2.3. Other Possible Modes of Action 4.7.2.4. Conclusions About the Hypothesized Mode of Action 4.8. SUSCEPTIBLE POPULATIONS AND LIFE STAGES 4.8.3. Other 10/8/2009 B-5 DO NOT CITE OR QUOTE ------- |